In recent decades, the role of hydrogen sulfide (H2S), a gas mediator and signaling agent, has been studied in the regulation of intercellular signaling and intracellular signal transduction pathways with various physiological and pathophysiological effects in cells and tissues. These cellular pathways are responsible for changes in metabolism, epigenetic, and cellular behavior. There are enzymatic and non-enzymatic pathways of endogenous hydrogen sulfide biosynthesis. Numerous studies have shown the diverse effects of H2S on the physiological processes of neurotransmission in the brain, vascular smooth muscle relaxation in synergy with nitric oxide (NO), apoptosis, autophagy, angiogenesis, aging, inflammation, redox system, manifestations of oxidative stress, protein, as well as bioenergetic effects and systemic bioregulatory effects, including ANS. Recently, it was shown that H2S signaling is often dysregulated in different dysfunctions. The effect of H2S on insulin secretion and protection of the heart, kidneys, and brain from ischemic damage, and hypoxia is known. The availability of H2S as a bioregulator has led to changes in cytoprotection, scavenger’s function, and antiinflammatory activities in the digestive system, as well as it could be a molecular target for the creating new safe hybrid compounds, esp., H2S-realized nonsteroidal anti-inflammatory drugs. Our recent research has shown a cytoprotective effect on the mucous membrane of the esophagus and stomach. Thiosulfate sulfurtransferase (TST, EC 2.8.1.1)-derived H2S plays an important role in maintaining redox balance but its effects on mesenteric integrity in aspects of age-related changes and during stress response or high-carbohydrate diet are still limited.

Introduction

Many clinical studies have proved the effectiveness of probiotics in metabolic disorders associated with insulin resistance. However, the impact of probiotic therapy on pancreatic β-cell function is ambiguous. The influence of probiotic supplementation vs. placebo on β-cell function in people with type 2 diabetes (T2D) was assessed in a double-blind, single-center, randomized, placebo-controlled trial (RCT).

Methods

Sixty-eight patients with T2D were selected for participation in the RCT. Patients were randomly allocated to consumption of live multistrain probiotics or a placebo for 8 weeks, administered as a sachet formulation in double-blind treatment. The primary main outcome was the assessment of β-cell function as change in C-peptide and HOMA-β (homeostasis model assessment-estimated β-cell function), which was calculated using the HOMA2 calculator (Diabetes Trials Unit, University of Oxford). Secondary outcomes were the changes in glycemic control-related parameters, anthropomorphic variables, and cytokines levels. Analysis of covariance was used to assess the difference between groups.

Results

Supplementation with live multiprobiotic was associated with slight significant improvement of β-cell function (HOMA-β increased from 32.48 ± 13.12 to 45.71 ± 25.18; p = 0.003) and reduction of fasting glucose level (13.03 ± 3.46 vs 10.66 ± 2.63 mmol/L and 234.63 ± 62.36 vs 192.07 ± 47.46 mg/dL; p < 0.001) and HbA1c (8.86 ± 1.28 vs 8.48 ± 1.22; p = 0.043) as compared to placebo. Probiotic therapy significantly affects chronic systemic inflammation in people with T2D by reducing pro-inflammatory cytokine levels.

Conclusions

Probiotic therapies modestly improved β-cell function in patients with T2D. Modulating the gut microbiota represents a new diabetes treatment and should be tested in more extensive studies.

Trial Registration

NCT05765292.